Project Summary Aging brings about a marked increase in the likelihood of becoming tired, or tiring faster during an activity with mental load. This common aging phenomenon is called central fatigability (CF), which has many adverse consequences, including cognitive decline, degraded performance in daily tasks (e.g., driving), reduced participation in intellectually beneficial activities, poor quality of life, or mobility restriction. CF can occur in almost any older adult and is distinct from the fatigue symptoms that often occur in individuals with certain neurologic or cardiac diseases. Accurately assessing CF is the first step in the development and assessment of efficacy of treatments to mitigate CF in the aging population. In this R21 application, we propose to develop laboratory tasks that can efficiently induce and precisely capture CF (i.e., CF-manipulation task) in older adults. A robust CF-manipulation task will need to address issues related to temporary neuroplasticity, the fronto-basal ganglia circuit, and executive load. However, these prerequisites have not been sufficiently addressed by existing traditional CF-manipulation tasks (e.g., n-back, stroop). We propose to make use of a neuroeconomics paradigm ? specifically, gambling tasks ? to induce and capture CF in older adults to address the shortcomings of existing CF operationalizations. We hypothesize that compared to traditional CF-manipulation tasks, the gambling tasks will more efficiently induce CF in older adults. We will conduct an observational study with a randomized cross-over design involving two visits to compare two gambling tasks (Iowa gambling task and balloon analogue risk task) with two traditional tasks (i.e., n-back and stroop) in inducing and assessing CF in 52 cognitively healthy older adults without pathological conditions that can produce fatigue symptoms. In each visit, diffusion tensor imaging will be performed at baseline to evaluate the structural connectivity of the fronto-basal ganglia circuit, and event-related BOLD fMRI will be performed during the gambling or traditional tasks to evaluate the dynamic change of functional connectivity of the circuit. By leveraging the essence of our previous laboratory-based neuroeconomics work in monkeys and younger adults, this bench-to-bedside translational application will identify a novel, clinically useful tool for assessing CF. This tool may aide in the development of new treatments or prevention strategies for CF. Since CF is potentially modifiable, addressing CF will provide an innovative pathway in maintaining cognitive and functional independence and quality of life in older adults.